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Chemical Structure| 494799-18-7

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Product Details of [ 494799-18-7 ]

CAS No. :494799-18-7
Formula : C16H19NO2
M.W : 257.33
SMILES Code : COC(=O)C1=CC=C2C(NC=C2C2CCCCC2)=C1
MDL No. :MFCD09833287

Safety of [ 494799-18-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H317
Precautionary Statements:P280

Application In Synthesis of [ 494799-18-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 494799-18-7 ]

[ 494799-18-7 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 494799-17-6 ]
  • [ 74-88-4 ]
  • [ 494799-18-7 ]
YieldReaction ConditionsOperation in experiment
92.6% With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 4h; To a stirred solution of compound C19 (0.5 g, 2.07 mmol) in DMF (6 mL), K2C03 (0.395 g, 2.85 mmol) and Mel (0.32 g, 2.26 mmol) were added. The resulting reaction mixture was stirred at RT for 4 h. The progress of the reaction was monitored by TLC. After completion,the reaction mixture was diluted with ice cold water (50 mL) and extracted with DCM (3 x 50 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford the crude compound 35 (0.49 g, 92.6percent) as a pale-yellow oil. The crude compound was used as such for the next step without further purification. TLC: 50percent EtOAc/ hexane (Rf: 0.6), ?H-NMR (400 MHz, CDC13): oe 8.17 (br.s, 1H), 8.12 (s, 1H), 7.79 (d,J= 8.4 Hz, 1H), 7.68 (d, J= 8.4 Hz, 1H), 7.13 (s, 1H), 3.90 (s, 3H), 2.86 ?2.84 (m, 1H), 2.12 ?2.06 (m, 2H), 1.86 ? 1.79 (m, 2H), 1.58 -1.43 (m, 4H), 1.38 ? 1.27 (m, 2H); LCMS Observed (m/z): 258 (M+1).
90% With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; A 2 L flask equipped with a dropping funnel and mechanical stirrer was charged with crude <strong>[494799-17-6]3-cyclohexyl-6-indole carboxylic acid</strong> (99.4 g, 0.409 mole) and anhydrous DMF (665 mL) was added followed by anhydrous potassium carbonate (78.13 g, 0.565 mole). lodomethane (63.72 g, 0.449 mole) was added dropwise over 35 min with stirring to the slurry which was then stirred overnight at room temperature until complete disappearance of starting material (TLC). The resulting suspension was then poured into water (1350 mL) and acidified to pH 4 with 4N HCI (200 mL). The product was extracted into ether (3 x 1700 mL), washed with water and brine and dried (NA2SO4). VOLATILES were removed under reduced pressure and the residue was triturated with hexane (700 mL). The beige solid was filtered and dried under vacuum (94.3 g, 90 percent yield).
  • 2
  • [ 494799-17-6 ]
  • [ 67-56-1 ]
  • [ 494799-18-7 ]
YieldReaction ConditionsOperation in experiment
100% With thionyl chloride; at 0℃; for 24h;Heating / reflux; Step 2; methy\\ 3-cvclohexyl-1H-indole-6-carboxylate; A solution (0.5 M) of 3-cyclohexenyl-1H-indole-6-carboxylic acid (from Step 1) in THF/M eOH (0.5 M, 1:1, v/v) was hydrogenated for 14 h over Pd(OH)2/C (0.1 eq., 20percent) at 60 psi. The catalyst was removed by filtration on a pad of celite.(TM). and the filtrate evaporated to dryness to afford 3-cyclohexyl-1 H-indoIe-6-carboxylic acid (90percent) as a white solid 1H NMR (300 MHz, DMSO-d6, 300 K) 6 1.20 -1.53 (m, SH), L70-L87 (m, 3H), 1.90-2.02 (m, 2H), 2.69-2.86 (m, 1H), 7.40 (s, 1H), 7.55-7.65 (rn, 2H), 8.0 (s, 1H), 11.40 (s, 1H); MS (ES+ m/z 244 (M+H)+. A solution of the foregoing compound in MeOH {0.4 M) was treated at 0 °C with thionylchloride (0.5 eq.) and refluxed for 24 h. Volatiles were removed under vacuum to afford the title compound (100percent) as a solid.
95% Step 5. 3-Cyclohexyl-1H-indole-6-carboxylic acid methyl ester (165) [0311] 63g (0.259mmole) 164 was dissolved in MeOH (1 L) and HCl (100 mL, 4M in dioxane) was added slowly. The mixture was refluxed for 3 hrs. The purple solution was then cooled and the solvents removed under vacuum. The residue was dissolved in EtOAc (500 mL), was washed with NaHCO3 (sat. 2 x 150 mL). The purple color was EPO <DP n="137"/>replaced with a light yellow one. The organic layer was further washed with saturated NaCl solution, dried (Na2SO4) and the solvents removed. The crude solid was recrystallized from a mixture of MeOH (2L) and water (500 mL). The crystals were recovered on a filter, washed with water and dried to yield compound 165 as a light yellow solid (63.8g, 95percent).
88% With thionyl chloride; for 48h;Heating / reflux; A 5 L three-necked flask was equipped with a reflux condenser and a mechanical stirrer, and the system was purged with nitrogen gas. The indole carboxylic acid from above (300.00 g, 1.233 mole) was charged into the flask and suspended in MEOH (2 L). Thionyl chloride (5 mL, 0.0685 mole, 0.05 equivalent) was added dropwise and the mixture was refluxed FOR 48 h. Volatiles were removed under reduced pressure and the residue was triturated with hexane to give a beige solid that was washed with hexane and dried under vacuum (279.6 g, 88percent yield).
69% With thionyl chloride; for 18h;Heating / reflux;Product distribution / selectivity; Methyl 3-cyclohexyl-1H-indole-6-carboxylate; Thionyl chloride (1 mL) was added to a stirred mixture of <strong>[494799-17-6]3-cyclohexyl-1H-indole-6-carboxylic acid</strong> (30.4 g, 0.125 mol) in methanol (300 mL). The mixture was stirred at reflux for 18 hours, treated with decolorizing carbon, and filtered. The filtrate was concentrated to about 150 mL at which point crystallization occurred. The filtrate was cooled to room temperature and filtered. The solid was washed with cold methanol followed by diethyl ether to provide the desired product as a pale purple solid (22.2 g, 69percent yield). ESI-MS m/z 258 (MH+); 1H NMR (300 MHz, CDCl3) delta 1.35 (m, 4H), 1.63 (s, 1H), 1.78 (m, 3H), 2.06 (d, J=8.05 Hz, 2H, 3.90 (m, 1H), 7.08 (d, J=1.83 Hz, 1H), 7.62 (s, 1H), 7.65 (s, 1H),7.74 (d, J=1.46 Hz, 1H), 7.77 (d, J=1.46 Hz, 1H), 8.08 (s, 1H).
69% With thionyl chloride; for 18h;Heating / reflux;Product distribution / selectivity; Methyl 3-cyclohexyl-1H-indole-6-carboxylate.; Thionyl chloride (1 mL) was added to a stirred mixture of <strong>[494799-17-6]3-cyclohexyl-1H-indole-6-carboxylic acid</strong> (30.4 g, 0.125 mol) in methanol (300 mL). The mixture was stirred at reflux for 18 hours, treated with decolorizing carbon, and filtered. The filtrate was concentrated to about 150 mL at which point crystallization occurred. The filtrate was cooled to room temperature and filtered. The solid was washed with cold methanol followed by diethyl ether to provide the desired product as a pale purple solid (22.2 g, 69percent yield). ESI-MS m/z 258 (MH+); 1H NMR (300 MHz, CDCl3) delta 1.35 (m, 4H), 1.63 (s, 1H), 1.78 (m, 3H), 2.06 (d, J=8.05 Hz, 2H, 3.90 (m, 1H), 7.08 (d, J=1.83 Hz, 1H), 7.62 (s, 1H), 7.65 (s, 1H), 7.74 (d, J=1.46 Hz, 1H), 7.77 (d, J=1.46 Hz, 1H), 8.08 (s, 1H).
69% thionyl chloride; for 18h;Heating / reflux; Methyl 3-cyclohexyl-1H-indole-6-carboxylate. Thionyl chloride (1 mL) was added to a stirred mixture of <strong>[494799-17-6]3-cyclohexyl-1H-indole-6-carboxylic acid</strong> (30.4 g, 0.125 mol) in methanol (300 mL). The mixture was stirred at reflux for 18 hours, treated with decolorizing carbon, and filtered. The filtrate was concentrated to about 150 mL at which point crystallization occurred. The filtrate was cooled to room temperature and filtered. The solid washed with cold methanol followed by diethyl ether to provide the desired product as a pale purple solid (22.2 g, 69percent yield). ESI-MS m/z 258 (MH+); 1H NMR (300 MHz, CDCl3.) d 1.35 (m, 4H), 1.63 (s, 1H), 1.78 (m, 3H), 2.06 (d, J=8.05 Hz, 2H, 3.90 (m, 1H), 7.08 (d, J=1.83 Hz, 1H), 7.62 (s, 1H), 7.65 (s, 1H), 7.74 (d, J=1.46 Hz, 1H), 7.77 (d, J=1.46 Hz, 1H), 8.08 (s, 1H).
69% With thionyl chloride; for 18h;Heating / reflux; Methyl 3-cyclohexyl-1H-indole-6-carboxylate. Thionyl chloride (1 mL) was added to a stirred mixture of Intermediate 4A (30.4 g, 0.125 mol) in methanol (300 mL). The mixture was stirred at reflux for 18 hours, treated with decolorizing carbon, and filtered. The filtrate was concentrated to about 150 mL at which point crystallization occurred. The filtrate was cooled to room temperature and filtered. The solid was washed with cold methanol followed by diethyl ether to provide the desired product as a pale purple solid (22.2 g, 69percent yield). ESI-MS m/z 258 (MH+); 1H NMR (300 MHz, CDCl3) delta 1.35 (m, 4H), 1.63 (s, 1H), 1.78 (m, 3H), 2.06 (d, J=8.05 Hz, 2H, 3.90 (m, 1H), 7.08 (d, J=1.83 Hz, 1H), 7.62 (s, 1H), 7.65 (s, 1H), 7.74 (d, J=1.46 Hz, 1H), 7.77 (d, J=1.46 Hz, 1H), 8.08 (s, 1H).
69% With thionyl chloride; for 18h;Heating / reflux;Product distribution / selectivity; Methyl 3-cyclohexyl-1H-indole-6-carboxylate.; Thionyl chloride (1 mL) was added to a stirred mixture of <strong>[494799-17-6]3-cyclohexyl-1H-indole-6-carboxylic acid</strong> (30.4 g, 0.125 mol) in methanol (300 mL). The mixture was stirred at reflux for 18 hours, treated with decolorizing carbon, and filtered. The filtrate was concentrated to about 150 mL at which point crystallization occurred. The filtrate was cooled to room temperature and filtered. The solid was washed with cold methanol followed by diethyl ether to provide the desired product as a pale purple solid (22.2 g, 69percent yield). ESI-MS m/z 258 (MH+); 1H NMR (300 MHz, CDCl3.) delta 1.35 (m, 4H), 1.63 (s, 1H), 1.78 (m, 3H), 2.06 (d, J=8.05 Hz, 2H, 3.90 (m, 1H), 7.08 (d, J=1.83 Hz, 1H), 7.62 (s, 1H), 7.65 (s, 1H),7.74 (d, J=1.46 Hz, 1H), 7.77 (d, J=1.46 Hz, 1H), 8.08 (s, 1H).
69% With thionyl chloride; for 18h;Heating / reflux;Product distribution / selectivity; Intermediate 18 Methyl 3-cyclohexyl-1H-indole-6-carboxylate. Thionyl chloride (1 mL) was added to a stirred mixture of <strong>[494799-17-6]3-cyclohexyl-1H-indole-6-carboxylic acid</strong> (30.4 g, 0.125 mol) in methanol (300 mL). The mixture was stirred at reflux for 18 hours, treated with decolorizing carbon, and filtered. The filtrate was concentrated to about 150 mL at which point crystallization occurred. The filtrate was cooled to room temperature and filtered. The solid was washed with cold methanol followed by diethyl ether to provide the desired product as a pale purple solid (22.2 g, 69percent yield). ESI-MS m/z 258 (MH+); 1H NMR (300 MHz, CDCl3.) delta 1.35 (m, 4H), 1.63 (s, 1H), 1.78 (m, 3H), 2.06 (d, J=8.05 Hz, 2H, 3.90 (m, 1H), 7.08 (d, J=1.83 Hz, 1H), 7.62 (s, 1H), 7.65 (s, 1H), 7.74 (d, J=1.46 Hz, 1H), 7.77 (d, J=1.46 Hz, 1H), 8.08 (s, 1H).
69% With thionyl chloride; for 18h;Heating / reflux;Product distribution / selectivity; Thionyl chloride (1 mL) was added to a stirred mixture of <strong>[494799-17-6]3-cyclohexyl-1H-indole-6-carboxylic acid</strong> (30.4 g, 0.125 mol) in methanol (300 mL). The mixture was stirred at reflux for 18 hours, treated with decolorizing carbon, and filtered. The filtrate was concentrated to about 150 mL at which point crystallization occurred. The filtrate was cooled to room temperature and filtered. The solid was washed with cold methanol followed by diethyl ether to provide the desired product as a pale purple solid (22.2 g, 69percent yield). ESI-MS m/z 258 (MH+); 1H NMR (300 MHz, CDC3) delta 1.35 (m, 4H), 1.63 (s, 1H), 1.78 (m, 3H), 2.06 (d, J=8.05 Hz, 2H, 3.90 (m, 1H), 7.08 (d, J=1.83 Hz, 1H), 7.62 (s, 1H), 7.65 (s, 1H), 7.74 (d, J=1.46 Hz, 1H), 7.77 (d, J=1.46 Hz, 1H), 8.08 (s, 1H).
55.2% With thionyl chloride; for 1h;Heating / reflux; Step C.Thionyl chloride (135 muL, 1.85 mmol) was added to a solution of 3-cyclohexylindole- 6-carboxylic acid (1-3, 1.80 g, 7.4 mmol) in methanol (20 mL). The resulting solution was heated to reflux for Ih, then allowed to cool down to room temperature. The reaction mixture was concentrated under vacuum. Then, the residue was partitioned between CH2Cl2 and ice-cold water, dried and evaporated to give 1.05 g (55.2 percent) of the target product 1-4: m/z = 258 (M+H)+.

  • 3
  • [ 50820-65-0 ]
  • [ 108-94-1 ]
  • [ 494799-18-7 ]
YieldReaction ConditionsOperation in experiment
85% Methyl 3-cyclohexyl-1H-indole-6-carboxylate; Cyclohexanone (42.46 mL, 0.40 mol) was added in a single portion to a stirred solution of <strong>[50820-65-0]methyl indole-6-carboxylate</strong> (47.8 g, 0.27 m) in dry dichloromethane (500 mL). The reaction mixture was then cooled to 10 C. and trifluoroacetic acid (63.13 mL, 0.8 m) was added dropwise followed by triethyl silane (174.5 mL, 1.09 m). Upon addition, the temperature was allowed to rise to rt, after which it was stirred for a further 12 h. Dichloromethane (200 mL) was then added and the reaction mixture was washed successively with with 10% sodium bicarbonate solution and brine. The organic layer dried over sodium sulfate, filtered and concentrated under vacuum. The resultant residuce was purified by flash chromatography on silica (60-120) using hexane-ethyl acetate (9.5:0.5) mixture as eluant. Homogeneous fractions were combined and evaporated to give 60 g of the desired product (85%). Analytical data on this material was consistant with that observed with a sample prepared by the alternative route described above.
85% Methyl 3-cyclohexyl-1H-indole-6-carboxylate.; Cyclohexanone (42.46 mL, 0.40 mol) was added in a single portion to a stirred solution of <strong>[50820-65-0]methyl indole-6-carboxylate</strong> (47.8 g, 0.27 m) in dry dichloromethane (500 mL). The reaction mixture was then cooled to 10 C. and trifluoroacetic acid (63.13 mL, 0.8 m) was added dropwise followed by triethyl silane (174.5 mL, 1.09 m). Upon addition, the temperature was allowed to rise to rt, after which it was stirred for a further 12 h. Dichloromethane (200 mL) was then added and the reaction mixture was washed successively with 10% sodium bicarbonate solution and brine. The organic layer dried over sodium sulfate, filtered and concentrated under vacuum. The resultant residuce was purified by flash chromatography on silica (60-120) using hexane-ethyl acetate (9.5:0.5) mixture as eluant. Homogeneous fractions were combined and evaporated to give 60 g of the desired product (85%). Analytical data on this material was consistant with that observed with a sample prepared by the alternative route described above.
85% Methyl 3-cyclohexyl-1H-indole-6-carboxylate.; Cyclohexanone (42.46 mL, 0.40 mol) was added in a single portion to a stirred solution of <strong>[50820-65-0]methyl indole-6-carboxylate</strong> (47.8 g, 0.27 m) in dry dichloromethane (500 mL). The reaction mixture was then cooled to 10 C. and trifluoroacetic acid (63.13 mL, 0.8 m) was added dropwise followed by triethyl silane (174.5 mL, 1.09 m). Upon addition, the temperature was allowed to rise to rt, after which it was stirred for a further 12 h. Dichloromethane (200 mL) was then added and the reaction mixture was washed successively with with 10% sodium bicarbonate solution and brine. The organic layer dried over sodium sulfate, filtered and concentrated under vacuum. The resultant residuce was purified by flash chromatography on silica (60-120) using hexane-ethyl acetate (9.5:0.5) mixture as eluant. Homogeneous fractions were combined and evaporated to give 60 g of the desired product (85%). Analytical data on this material was consistant with that observed with a sample prepared by the alternative route described above.
85% With triethylsilane; trifluoroacetic acid; In dichloromethane; at 10 - 20℃; for 12h;Product distribution / selectivity; Intermediate 20 Methyl 3-cyclohexyl-1H-indole-6-carboxylate. Cyclohexanone (42.46 mL, 0.40 mol) was added in a single portion to a stirred solution of <strong>[50820-65-0]methyl indole-6-carboxylate</strong> (47.8 g, 0.27 m) in dry dichloromethane (500 mL). The reaction mixture was then cooled to 10 C. and trifluoroacetic acid (63.13 mL, 0.8 m) was added dropwise followed by triethyl silane (174.5 mL, 1.09 m). Upon addition, the temperature was allowed to rise to rt, after which it was stirred for a further 12 h. Dichloromethane (200 mL) was then added and the reaction mixture was washed successively with 10% sodium bicarbonate solution and brine. The organic layer dried over sodium sulfate, filtered and concentrated under vacuum. The resultant residue was purified by flash chromatography on silica (60-120) using hexane-ethyl acetate (9.5:0.5) mixture as eluant. Homogeneous fractions were combined and evaporated to give 60 g of the desired product (85%). Analytical data on this material was consistant with that observed with a sample prepared by the alternative route described above.
85% With triethylsilane; trifluoroacetic acid; In dichloromethane; at 10 - 20℃; for 12h;Product distribution / selectivity; Cyclohexanone (42.46 mL, 0.40 mol) was added in a single portion to a stirred solution of <strong>[50820-65-0]methyl indole-6-carboxylate</strong> (47.8 g, 0.27 m) in dry dichloromethane (500 mL). The reaction mixture was then cooled to 10 C. and trifluoroacetic acid (63.13 mL, 0.8 m) was added dropwise followed by triethyl silane (174.5 mL, 1.09 m). Upon addition, the temperature was allowed to rise to rt, after which it was stirred for a further 12 h. Dichloromethane (200 mL) was then added and the reaction mixture was washed successively with with 10% sodium bicarbonate solution and brine. The organic layer dried over sodium sulfate, filtered and concentrated under vacuum. The resultant residuce was purified by flash chromatography on silica (60-120) using hexane-ethyl acetate (9.5:0.5) mixture as eluant. Homogeneous fractions were combined and evaporated to give 60 g of the desired product (85%). Analytical data on this material was consistant with that observed with a sample prepared by the alternative route described above.

  • 4
  • [ 494799-17-6 ]
  • [ 494799-18-7 ]
YieldReaction ConditionsOperation in experiment
68% To a solution of S-cyclohexyl-I H-indole-psi-carboxylic acid Intermediate 61 (900 mg, 3.7 mmol) in methanol was added HCI gas. The mixture was stirred at 75°C for 18 hours. The solvent was evaporated and the residue was diluted with water and NaOH and extracted <n="69"/>with diethyl ether. The organic phase was dried over Na2SO4, filtered and evaporated to give the title compound as orange beige solid (650 mg, 68percent).NMR1H NMR (300 MHz), , delta : 8.03 (s, 1 H), 7.71 (dd, 1 H), 7.59 (d, 1 H), 7.04 (s, 1 H), 3.86 (s, 3H), 2.77 (m, 1 H), 2.02 (m, 2H), 1.77 (m, 3H), 1.40 (m, 5H).
  • 5
  • [ 494799-18-7 ]
  • [ 494799-17-6 ]
 

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